Combined Action of Anti-MUC1 Monoclonal Antibody and Pyrazole-Platinum(II) Complexes Reveals Higher Effectiveness towards Apoptotic Response in Comparison with Monotherapy in AGS Gastric Cancer Cells
MUC1 mucin is a transmembrane glycoprotein aberrantly overexpressed and underglycosylated in most epithelium origin cancers. Combining chemotherapeutics with monoclonal antibodies toward cancer-related antigens is one of the new strategies in cancer therapies. In this study, we assessed the effectiv...
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| Main Authors: | , , , |
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| Format: | Book |
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MDPI AG,
2021-06-01T00:00:00Z.
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| Summary: | MUC1 mucin is a transmembrane glycoprotein aberrantly overexpressed and underglycosylated in most epithelium origin cancers. Combining chemotherapeutics with monoclonal antibodies toward cancer-related antigens is one of the new strategies in cancer therapies. In this study, we assessed the effectiveness of 10 μM cisplatin (cisPt), two pyrazole-platinum(II) complexes (PtPz4 and PtPz6), and 5 μg/mL anti-MUC1 used as monotherapy, as well as cisplatin and its derivatives combined with mAb on apoptotic response and specific cancer-related sugar antigens in AGS gastric cancer cells. Flow cytometry, RT-PCR, Western blotting, and ELISA tests were applied to determine the influence of examined compounds on analyzed factors. PtPz6 combined with anti-MUC1 revealed the strongest apoptotic response compared to control and monotherapy. The combined action of both cisPt derivatives and anti-MUC1 was more effective than monotherapy in relation to <i>Bad, Bcl-xL, Bcl-2, caspase-9, caspase-3</i>, as well as pro- and cleaved <i>caspase-3</i> protein, and T, sialyl Tn sugar antigens in cell lysates, and Tn, T, sialyl Tn, sialyl T antigens in culture medium. Additionally, PtPz4 administrated with mAb was revealed to be more potent than used alone with regard to <i>Bax</i> protein and <i>Bid</i> expression, and PtPz6 used in complex with anti-MUC1 revealed more efficient action towards <i>Akt</i> and sialyl T antigen expression. These data indicate the rationality of the potential application of combined treatment of anti-MUC1 and cisPt derivatives in gastric cancer therapy. |
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| Item Description: | 10.3390/pharmaceutics13070968 1999-4923 |